Our studies aim to elucidate in biochemical terms the influence of perinatal exposure to a model aromatic polycyclic hydrocarbon carcinogen on the development of liver and lung enzymes which are responsible for the metabolism of a variety of drugs and chemicals. Alterations in this mixed-function oxidase enzyme system have been related to susceptibility to certain chemicals which are metabolized to the proximate carcinogen. We have found that perinatal exposure of mice produces alterations in basal levels of this system and in the inducibility when exposed to chemicals, such as phenobarbital and 3-methylcholanthrene (3-MC), which are known to alter the activity of the mixed function oxidases. We plan to relate these biochemical changes to development of local, lung, and liver tumors following challenge with 3-MC at various postnatal ages. The second area of our work relates to the inhibition of drug metabolism seen following treatment with killed suspensions of Corynebacterium parvum. We hope to define the mechanism(s) by which such immunomodulators affect drug metabolism. Furthermore, we will attempt to relate such changes in metabolism to the development of tumors in mice in the groups exposed either transplacentally or via suckling to 3-MC and/or its metabolites. BIBLIOGRAPHIC REFERENCES: Soyka, L.F., Hunt, W.G. and Knight, S.E. Differential effects of pre- vs. postnatal exposure to 3-methylcholanthrene on hepatic and lung drug metabolizing activity and tumorigenesis. Fed. Proc. 36: 305, 1977 (Abst). Iba, M., Soyka, L.F., and Schulman, M.P. Characteristics of hepatic mixed function oxidase system of the neonatal rat. Fed. Proc. 36: 1033, 1977 (Abst).